4-amino-2-chloromethyl-6,7-dimethoxyquinazoline | 1443358-77-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: 4-amino-2-chloromethyl-6,7-dimethoxyquinazoline
• 英文别名: 2-(Chloromethyl)-6,7-dimethoxyquinazolin-4-amine；2-(chloromethyl)-6,7-dimethoxyquinazolin-4-amine
• CAS: 1443358-77-7
• 化学式: C₁₁H₁₂ClN₃O₂
• 分子量: 253.688
• InChiKey: YTBFMJRFKLCOHB-UHFFFAOYSA-N

物化性质

• 沸点：
  347.4±42.0 °C(Predicted)
• 密度：
  1.349±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  17
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  70.3
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  二苯甲基哌嗪 、 4-amino-2-chloromethyl-6,7-dimethoxyquinazoline 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以75%的产率得到4-amino-2-[(4-benzhydryl)piperazin-1-ylmethyl]-6,7-dimethoxyquinazoline
  参考文献：
  名称：

  6,7-二甲氧基衍生物作为双重作用的探讨α 1 -和AT 1受体拮抗剂：合成，评价，药效及3D-QSAR建模和受体对接研究†

  摘要：

  6,7-二甲氧基支架进一步探索了α提供双重作用的1 -和AT 1通过合成一系列衍生物和生物学评价新合成的化合物受体拮抗剂。根据目前的化合物的生物数据和此前报道的化合物，药效模型，用于开发α 1 -和AT 1-受体拮抗剂的活性。随后，还导出了两种受体的拮抗作用的3D-QSAR模型。使用各种统计参数对开发的3D-QSAR模型进行了验证，并且使用特拉唑嗪和哌唑嗪作为外部化合物进一步验证了两种开发模型。对接研究证实受体-配体稳定平衡-双活性拮抗剂（的相互作用110在两个α的活性位点）1 -以及AT 1 -受体，这些都是由同源性建模所获得的结构。两个（42和110从新合成的衍生物的化合物的）所提供的最高效力（p阿2为α 1=分别为9.45和8.77，以及AT 1分别为8.36和8.60），并且两个受体的平衡调节。既发现本化合物是特拉唑嗪略小有力作为α 1 -拮抗剂和等效氯沙坦如AT 1 -拮抗剂在体内动物模型。

  DOI：

  10.1039/c6ra00589f
• 作为产物：
  描述：

  6-硝基藜芦酸 在 氯化亚砜 、 氨 、 铁粉 、 氯化铵 、 正丁胺 、 三氯氧磷 作用下， 生成 4-amino-2-chloromethyl-6,7-dimethoxyquinazoline
  参考文献：
  名称：

  Design and synthesis of 6,7-dimethoxyquinazoline analogs as multi-targeted ligands for α1- and AII-receptors antagonism

  摘要：

  Multiple-targeted ligands can have certain advantages for the management of hypertension which has multiple controls. Molecules with dual bioactivities are available in literature for treating metabolic disorders like diabetes, hypertension and hypercholesterolemia. After scrutinizing the SAR of prazosin-type alpha(1)-blockers and AII-antagonists it was planned to develop dual alpha(1)- and AII-antagonists. Five series of quinazoline derivatives were synthesized and evaluated as dual alpha(1)- and AII-antagonists on rat aortic strips for the blockade of known alpha(1)- and AII-agonist mediated contractions. Many compounds showed balanced activity on both the receptors but compound (22) was found to be the most active derivative having higher antagonistic activity on both the receptors. In the in vivo experiments the chosen compound (22) was slightly less active than prazosin but was found to be equipotent to losartan. These findings shed a new light on the structural requirements for both alpha(1)- as well as AII-receptor antagonists. (c) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.04.054

文献信息

• Design and synthesis of 6,7-dimethoxyquinazoline analogs as multi-targeted ligands for α1- and AII-receptors antagonism
  作者：M.R. Yadav、P.P. Naik、H.P. Gandhi、B.S. Chauhan、R. Giridhar

  DOI：10.1016/j.bmcl.2013.04.054

  日期：2013.7

  Multiple-targeted ligands can have certain advantages for the management of hypertension which has multiple controls. Molecules with dual bioactivities are available in literature for treating metabolic disorders like diabetes, hypertension and hypercholesterolemia. After scrutinizing the SAR of prazosin-type alpha(1)-blockers and AII-antagonists it was planned to develop dual alpha(1)- and AII-antagonists. Five series of quinazoline derivatives were synthesized and evaluated as dual alpha(1)- and AII-antagonists on rat aortic strips for the blockade of known alpha(1)- and AII-agonist mediated contractions. Many compounds showed balanced activity on both the receptors but compound (22) was found to be the most active derivative having higher antagonistic activity on both the receptors. In the in vivo experiments the chosen compound (22) was slightly less active than prazosin but was found to be equipotent to losartan. These findings shed a new light on the structural requirements for both alpha(1)- as well as AII-receptor antagonists. (c) 2013 Elsevier Ltd. All rights reserved.
• Exploration of 6,7-dimethoxyquinazoline derivatives as dual acting α₁- and AT₁-receptor antagonists: synthesis, evaluation, pharmacophore & 3D-QSAR modeling and receptor docking studies
  作者：Neetesh Agrawal、Jatin Machhi、Virendra Rathwa、Ashish M. Kanhed、Sagar Patel、Prashant Murumkar、Hardik Gandhi、Mange Ram Yadav

  DOI：10.1039/c6ra00589f

  日期：——

  ne scaffold was further explored to provide dual acting α1- and AT1-receptor antagonists by synthesizing a series of derivatives and biologically evaluating the newly synthesized compounds. Based on the biological data of the current compounds and the earlier reported compounds, pharmacophore models were developed for α1- and AT1-receptor antagonist activities. Subsequently, 3D-QSAR models were also

  6,7-二甲氧基支架进一步探索了α提供双重作用的1 -和AT 1通过合成一系列衍生物和生物学评价新合成的化合物受体拮抗剂。根据目前的化合物的生物数据和此前报道的化合物，药效模型，用于开发α 1 -和AT 1-受体拮抗剂的活性。随后，还导出了两种受体的拮抗作用的3D-QSAR模型。使用各种统计参数对开发的3D-QSAR模型进行了验证，并且使用特拉唑嗪和哌唑嗪作为外部化合物进一步验证了两种开发模型。对接研究证实受体-配体稳定平衡-双活性拮抗剂（的相互作用110在两个α的活性位点）1 -以及AT 1 -受体，这些都是由同源性建模所获得的结构。两个（42和110从新合成的衍生物的化合物的）所提供的最高效力（p阿2为α 1=分别为9.45和8.77，以及AT 1分别为8.36和8.60），并且两个受体的平衡调节。既发现本化合物是特拉唑嗪略小有力作为α 1 -拮抗剂和等效氯沙坦如AT 1 -拮抗剂在体内动物模型。